This partnership will bridge the technology development efforts of Caltech faculty in Applied Physics and Bioengineering with clinical needs of faculty at the USC Keck School of Medicine. We will apply technology for nanofluidic chips that has been developed at Caltech to problems of biological and medical interest. Using the combined resources of the Applied Physics and the Bioengineering programs, we will develop new nanotechnology to solve a number of bioengineering obstacles that presently exist for single cell genomic analysis on a chip. We will develop microfabricated chips with the ability to manipulate nanoliters of fluid; these chips will be used to perform highly parallel biochemical manipulations and genetic analyses of rare populations of cells. The chips will be able to create unique reagents that can be analyzed using conventional functional genomics techniques. A chip foundry will be created in order to produce research quantities of these chips that can be shared among collaborators. The chip technology will be used to investigate the following two problems of particular medical importance: factor and marker discovery in haematopoietic stem cells, and the discovery and characterization of unculturable pathogens in the human gut.